This invention relates to electrical imaging technology, and more specifically to an apparatus and method for producing high resolution images, with accurate values of the electrical properties of objects, such as the human breast, which are substantially homogeneous in composition except for inhomogeneities such as tumors.
The demand for new medical imaging modalities is driven by the need to identify tissue characteristics that are not currently identifiable using existing imaging modalities. After lung cancer, breast cancer remains the deadliest cancer for women, taking the lives of approximately 40,200 women in 2001 according to National Cancer Institute. There were 192,000 new breast cancer cases in 2001. Approximately 28 million women in the US are screened for breast cancer each year.
A high percentage of breast cancers are not detected at the screening stage. Studies show that 20% to 50% of breast cancers go undetected at the screening stage. The motivation for early detection is great: breast cancer detected in the early stage has an average cost of treatment of $11,000 and a 5 year survival rate of approximately 96%, while late stage breast cancer costs $140,000 on average to treat and the 5 year survival falls to 20%. Medical professionals often rely on expensive biopsies to determine cancerous tissues. These procedures are neither fast nor patient-friendly. Radiation treatment of cancerous tumors is applied broadly and excessively throughout the region of the tumor to insure complete cancerous cell destruction. Clearly, there is a need for better imaging technologies for breast cancer detection and for real-time tracking of cancer call destruction during radiation treatment procedures.
X-ray mammography is the preferred modality for breast cancer detection. With the development of digital systems, and the use of computer-aided diagnosis (CAD) that assists physicians in identifying suspicious lesions by scanning x-ray films, a large increase in mammography system sales is expected. However, as noted previously, a large number of cancers are not detected using x-ray mammography, and to reduce x-ray exposure, breast compression techniques are used which make the examination painful.
After a suspicious lesion is found, the standard procedure is to perform a biopsy. Surgical biopsy is recommended for suspicious lesions with a high chance of malignancy but fine-needle aspiration cytology (FNAC) and core biopsy can be inexpensive and effective alternatives. Both FNAC and core biopsy have helped to reduce the number of surgical biopsies, sparring patients anxiety and reducing the cost of the procedure. However, core biopsies have often failed to show invasive carcinoma and both FNAC and core biopsies can result in the displacement of malignant cells away from the target—resulting in misdiagnosis.
According to the American Cancer Society, approximately 80% of breast biopsies are benign. Because of this, new less invasive technologies have been developed including: terahertz pulse imaging (TPI); thermal and optical imaging techniques including infrared; fluorescent and electrical impedance imaging. For the most part, these technologies are being pursued as an adjunct to traditional imaging modalities including computed tomography, magnetic resonance imaging, positron emission tomography, ultrasound and hybrid systems such as PET-CT.
The biochemical properties of cancerous cells versus normal cells are characterized by three factors: increased intracellular content of sodium, potassium, and other ions; increased intracellular content of water; and a marked difference in the electrochemical properties of the cell membranes. The increased intracellular concentrations of sodium, potassium and other ions results in higher intracellular electrical conductivity. Likewise, the increased water content results in higher conductivity when fatty cells surround the cancerous cells, since water is a better conductor than fat. And finally, the biochemical differences in the cell membranes of cancerous cells result in greater electrical permittivity.
A study of breast carcinoma described three separate classifications of tissue: tumor bulk, infiltrating margins, and distant (normal) tissue. The center of the lesion is called the tumor bulk and it is characterized by a high percentage of collagen, elastic fibers, and many tumor cells. Few tumor cells and a large proportion of normally distributed collagen and fat in unaffected breast tissue characterize the infiltrating margins. Finally, the distant tissues (2 cm or more from the lesion) are characterized as normal tissue.
The characterization of cancerous tissue is divided into two groups: in situ and infiltrating lesions. In situ lesions are tumors that remain confined in epithelial tissue from which they originated. The tumor does not cross the basal membrane, thus the tumor and the healthy tissue are of the same nature (epithelial). The electrical impedance of an in situ lesion is thus dependent on the abundance of the malignant cells that will impact the macroscopic conductivity (which is influenced by the increase in sodium and water) and permittivity (which is influenced by the difference in cell membrane electrochemistry).
By contrast, infiltrating lesions are tumors that pass through the basal membrane. The malignant tissue has a different nature than normal tissue (epithelial vs. adipose). Epithelial tissue is compact and dense. Adipose tissue is composed of large cells that are mostly triglycerides. These structural differences have the following impact. First the normal tissue has a lower cellular density. Second, cell liquid of normal tissue is not as abundant as epithelial cells. Generally the radiuses of epithelial cells are less than adipose cells, from which we conclude that the radius of cancerous cells is less than for normal cells. The impact on the fractional volume of cancerous cells vs. normal cells is that the fractional volume of cancerous cells is greater than for normal cells. The reason is that the epithelial population is higher than for normal, adipose cells. Finally, we note that intracellular conductivity of cancerous cells is greater than for intracellular conductivity of normal cells. Also, extracellular conductivity is higher because of the abundance of the extracellular fluid (because of larger gaps between normal and cancerous cells). Thus, the conductivity of the infiltrated tissue will be greater than for normal tissue.
Since the 1950's several researchers have measured and tabulated the electrical properties of biological tissues. The electrical properties (conductivity and permittivity) of human tissues exhibit frequency dependence (dispersion). There are three dispersion regions (α, β, and γ) at frequencies ranging from D.C. to 1 GHz. These dispersions in tissues are dependent on the number of cells, the shape of the cells, and their orientation, as well as the chemical composition of the tissue (i.e. composition and ionic concentrations of interstitial space and cytoplasm).
Various studies show that the values of biological tissues resistivities vary for a host of reasons. Cancerous tumors, for instance, possess two orders of magnitude (factor of 100) higher conductivity and permittivity values than surrounding healthy tissue. The application of medical treatments also produces a change in the electrical properties of tissue. For muscle tissue treated with radiation measurable changes to tissue impedance is reported. Significant changes occur in electrical impedance of skeletal muscle at low frequencies during hyperthermia treatment, and this change of electrical properties foreshadows the onset of cell necrosis.
Electrical impedance tomography (EIT) is a process that maps the impedance distribution within an object. This map is typically created from the application of current and the measurement of potential differences along the boundary of that object. There are three categories of EIT systems: current injection devices, applied potential devices, and induction devices. Henderson and Webster first introduced a device known as the impedance camera that produced a general map of impedance distribution. The Sheffield System and its incarnations were the first generation EIT system. In the later 80's, Li and Kruger report on an induced current device. In such a system, a combination of coils is placed around the object under test. A changing current in the coils produces a varying magnetic field that in turn induces a current in the object under test. As with the other drive method, electrodes are placed on the boundary of the object to measure the potential drops along the boundary.
Such electrical property imaging techniques are often referred to as “impedance tomography.” Most conventional electrical property imaging techniques are based on the premises that: 1) electrodes, or sensors, should be attached directly to the sample to be measured (for medical applications, the sample is a human body), and 2) current is injected sequentially through each electrode into the sample and the subsequent voltages measured. Therefore, these conventional imaging techniques implement a “constant current/measured voltage” scheme.
In a departure from such conventional electrical property imaging techniques, one of the present inventors arranged sensors in an array outside the object to be measured as disclosed in U.S. Pat. No. 4,493,039. Further, during imaging of a sample, ac voltages were applied at a fixed amplitude while the current was measured. This approach was further improved as described in pending patent application WO 99/12470 by filling the space between the object and the sensor array with an impedance matching medium. In addition, two techniques for computing the internal charge distribution based on the measured surface charges are described, referred to as the scale factor technique and the iterative technique. Both the iterative and scale factor technique require initial estimates of the geometry of internal structures derived from an associated imaging system such as an x-ray CT system. The iterative technique also requires an initial guess of the electrical properties of each region, and a forward calculation of the expected currents at the boundary to check the validity of the guess is then performed. This process is iterated until the guess produces boundary currents close to the measured values. The scale factor technique creates a “look up” table or neural net algorithm that allows one to correlate electrical properties or the interior of the sample with externally measured parameters using a large data set of model calculations. Because of limitations of the model and the need to extrapolate results to keep the size of the data sets reasonable, the scale factor technique has limited accuracy, but it does not require prior knowledge of approximate sample electrical properties. In fact, the results of the scale factor computation may serve as an initial estimate for the iterative technique. Both techniques are computationally intensive.